A phase I/II study of pembrolizumab (P) with gemcitabine (G) in patients (Pts) with previously-treated advanced non-small cell lung cancer (NSCLC): Phase I safety results.

Abstract

e20605 Background: P, an anti-PD1 antibody active in advanced NSCLC, has optimal benefit in tumors with high PD-L1 expression. G may increase antigen cross-presentation and prime CD8 T cell responses via increased tumor cell apoptosis. The combination of antigen cross-presentation and T cell activation may have a synergistic effect with concurrent anti-PD1 immunotherapy. This study is evaluating P + G in pts with previously-treated advanced NSCLC with goal to establish feasible dosing prior to phase II evaluation. Methods: The phase I portion enrolled sequential cohorts of 2 pts each with advanced NSCLC (1-3 prior lines of therapy), regardless of PD-L1 status. Treatment consisted of G, 1250 mg/m2, Days (D) 1 & 8 + P 200 mg D 1; 21-day cycles. Pts received G to max 6 cycles, P to max 2 years. Each cohort closed until pts completed 6 weeks therapy (2 cycles). Dose limiting toxicity (DLT) was defined as Gr 4 hematologic or Gr 3/4 non-hematologic toxicity at least possibly treatment-related within the first 6 weeks. Dose de-escalation would occur if ≥ 2 related DLTs occurred in the first 6 pts (accrual 6-36 pts); de-escalation was allowed for each drug independently based on toxicity attribution. Tumor tissue was collected for central PD-L1 testing and immune score analysis. Exploratory analysis of immune response via protein array and whole blood immunophenotyping is pending. Results: 6 pts were enrolled. Male/Female: 2/4; Age 53-73 (Median 67.5); ECOG 0/1: 1/5 pts, respectively. Median prior lines of therapy: 1 (Range 1-3). DLT: Gr 4 pulmonary hemorrhage with respiratory failure (1 pt, related to G). Other toxicities in DLT period: Gr 3 neutropenia (1), anemia (2 events in 1 pt). Other toxicities were Gr 1/2. 1 pt developed Gr 3 pneumonitis after DLT period ended (after cycle 3) and was removed from study treatment. Median cycles: 4 (Range 2-8). Primary reason for discontinuation was progression (4 pts). PD-L1 results by central analysis are pending. Conclusions: 1 DLT was observed in phase I; de-escalation was not triggered and the combination is considered feasible for phase II evaluation with G 1250 mg/m2 and P 200 mg (enrolling). Clinical trial information: NCT02422381.